Introduction: The rapid decline in MRI detected apparent diffusion coefficient (ADC) of brain tissue during ischemia is thought to be due to cytotoxic edema following energy failure resulting from the cessation of blood flow. This study aims to correlate rapidly acquired ADC measurements with DC electrical potential (as an indicator of cell membrane polarization) during global ischemia by cardiac arrest. Methods: Male Sprague-Dawley rats were anesthetized with halothane. A chlorided silver electrode was placed on the cortex through a burr hole, to measure brain DC potentials. DC and MABP were recorded continuously. MRI was performed on a 2.0T GE Omega system using echo planar imaging. Diffusion and non-diffusion weighted images were alternated to measure ADC over the brain every 6 seconds. Three groups of animals were defined: normal, hyperglycemic and hypoglycemic. Images were acquired continuously before and up to 15 minutes after cardiac arrest by i.v. KCl injection. Results: MABP fell to zero within 5 seconds of KCl injection. ADC immediately began to decline slowly, followed by a sudden and large decline and then remained constant or declined slowly again until the end of the scan. The delay between MABP drop and the rapid ADC decline in each group was (mean1s.d. minutes): normal 1.4210.17 (n=7), hyperglycemic 2.8510.83 (n=5), hypoglycemic 0.9410.39 (n=5). Corresponding values for the DC drop were: normal 1.4210.8 (n=5), hyperglycemic 3.5010.76 (n=3), hypoglycemic 0.6210.17 (n=2). Conclusion: A gradual ADC decline begins immediately upon MABP decrease, which may be due to an instantaneous transmembrane water shift. A subsequent rapid drop in ADC occurs coincident with anoxic cell membrane depolarization; both changes were delayed or accelerated together by hyper- or hypoglycemia.